title: Failure of a VapA/CpG oligodeoxynucleotide vaccine to protect foals against experimental Rhocococcus equi pneumonia despite induction of VapA-specific antibody and interferon-γ response.
abstract: We evaluated the immunogenic and protective potential of a recombinant VapA/CpG oligodeoxynucleotide (ODN) 2395 vaccine in neonatal foals undergoing experimental Rhodococcus equi challenge. Foals (n = 8) were vaccinated by intramuscular injection on days 1 and 15 of the study; control foals (n = 7) received a phosphate-buffered saline (PBS) solution. All foals were challenged by intrabronchial administration of 5 × 10⁶ R. equi 103⁺ on day 29. Bronchoalveolar lavages were done on days 15, 29, and 36 and total cell count, differential cell count, rVapA-stimulated cell proliferation and interferon (IFN)-γ mRNA expression determined. Clinical examination, complete blood (cell) counts, serology for VapA-specific antibodies, and culture of nasal and fecal swabs were done on days 1, 15, 29, 36, 43, and 50. Foals were humanely euthanized on day 50 and severity of pneumonia scored on a 4-point scale. Vaccination resulted in a significant increase in VapA-specific immunoglobulin (Ig) production, with total IgG and IgG(T) being increased by day 15. Expression of VapA-specific IFN-γ mRNA by BAL cells was increased in the vaccinated foals following challenge. Postmortem lung severity scores did not differ between groups. Two foals shed virulent R. equi in feces; however, real-time polymerase chain reaction (PCR) revealed the isolates to be different from the challenge strain.
authors.affiliation: Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan (Lohmann, Manning, Marques, Sangster, Townsend); Vaccine & Infectious Disease Organization (VIDO)-International Vaccine Centre (Inter-Vac), University of Saskatchewan, 120 Veterinary Road, Saskatoon, Saskatchewan (Lopez, Brownlie, Mutwiri, Gerdts, Potter, Townsend); Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan (Allen).
authors.forename: Katharina L
authors.initials: KL
authors.lastname: Lohmann
authors.forename: A Marianela
authors.initials: AM
authors.lastname: Lopez
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Manning
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Marques
authors.forename: Robert
authors.initials: R
authors.lastname: Brownlie
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Allen
authors.forename: Anna E
authors.initials: AE
authors.lastname: Sangster
authors.forename: George
authors.initials: G
authors.lastname: Mutwiri
authors.forename: Volker
authors.initials: V
authors.lastname: Gerdts
authors.forename: Andrew
authors.initials: A
authors.lastname: Potter
authors.forename: Hugh G G
authors.initials: HG
authors.lastname: Townsend
mesh_terms: D000193:Actinomycetales Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control / Q000662:veterinary*; D000818:Animals; D000831:Animals, Newborn; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology* / Q000592:standards; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D006734:Horse Diseases / Q000276:immunology / Q000382:microbiology* / Q000517:prevention & control; D006736:Horses; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D016014:Linear Models; D008297:Male; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000276:immunology; D011014:Pneumonia / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control / Q000662:veterinary*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D016929:Rhodococcus equi / Q000235:genetics / Q000276:immunology*; D014611:Vaccination / Q000592:standards / Q000662:veterinary*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000592:standards
chemical_list: D001426:Bacterial Proteins; D001428:Bacterial Vaccines; C527702:CpG ODN 2395; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D014614:Vaccines, Synthetic; C541879:VapA protein, Rhodococcus equi; D007371:Interferon-gamma